Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Low-Dose Nitrite Alleviates Early Effects of an X-ray Contrast Medium on Renal Hemodynamics and Oxygenation in Rats

Seeliger, Erdmann MD*; Cantow, Kathleen DVM*; Arakelyan, Karen MD*†; Ladwig, Mechthild DVM*; Persson, Pontus B. PhD*; Flemming, Bert MD*

doi: 10.1097/RLI.0b013e3182a6fea6
Original Articles

Objective Renal tissue hypoperfusion and hypoxia are pivotal pathophysiological elements in contrast media (CM)–induced acute kidney injury (AKI). According to a new paradigm of hypoxic vasodilation, nitrite is reduced to vasodilatory nitric oxide by hemoglobin in hypoxic areas. Here, we study the potential of low-dose nitrite administration to alleviate CM-induced AKI.

Materials and Methods In anesthetized rats, arterial blood pressure, total renal blood flow, cortical and medullary erythrocyte flux and oxygen tension (pO2), hindquarter blood flow, and methemoglobin were measured. Nitrite was continuously infused (0.172 mg/h per kilogram of body mass for 10 minutes; thereafter, 0.057 mg/h per kilogram of body mass); control rats received isotonic saline. Hypoxic vasodilation was studied through a brief period of hypoxia (10% inspiratory oxygen fraction). Then, 1.5 mL of the CM, iodixanol of 320 mg I/mL, was injected into the thoracic aorta and the effects studied for 60 minutes.

Results Nitrite infusion slightly increased methemoglobin, but it did not change per se any other parameter including arterial pressure. However, nitrite enhanced the hypoxic vasodilation in the kidney and hindquarter (by 100% and 70%, respectively) during the brief hypoxic challenge. In the control rats, CM resulted in renal tissue hypoxia mainly because of renal vasoconstriction. Medullary and cortical pO2 dropped upon CM injection and remained 30% to 40% below pre-CM level throughout the observation period. Nitrite infusion improved renal tissue oxygenation mainly by hindering CM-induced renal vasoconstriction. After a small transient drop (<25% for <5 minutes), medullary and cortical pO2 was restored to values indistinguishable from pre-CM levels.

Conclusions Low-dose nitrite infusion greatly alleviates early adverse effects of CM on renal tissue oxygenation in rats. Nitrite’s beneficial effect probably relies on its reduction to nitric oxide in hypoxic tissue with ensuing vasodilation. Our nitrite dose resulted in a negligible increase in methemoglobin and did not induce hypotension. Thus, low-dose nitrite infusion might prove to be a reasonably specific measure to reduce the risk for CM-induced AKI.

From the *Institut für Vegetative Physiologie, Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Campus Mitte; and †Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Berlin, Germany.

Received for publication June 18, 2013; and accepted for publication, after revision, July 26, 2013.

Conflicts of interest and sources of funding: Supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; FOR 1368, Se 998/3-1).

The authors report no conflicts of interest.

Reprints: Erdmann Seeliger, MD, Institut für Vegetative Physiologie, Charité CCM, Hessische St 3-4, 10115 Berlin, Germany. E-mail:

© 2014 by Lippincott Williams & Wilkins